Acetylation Research Articles

Lysine acetylation of histone acetyltransferase adaptor protein ADA2 is a mechanism of metabolic control of chromatin modification in plants.

Histone acetylation is a predominant active chromatin mark deposited by histone acetyltransferases (HATs) that transfer the acetyl group from acetyl coenzyme A (acetyl-CoA) to lysine ε-amino groups in histones. GENERAL CONTROL NON-REPRESSED PROTEIN 5 (GCN5) is one of the best-characterized HATs and functions in association with several adaptor proteins such as ADA2 within multiprotein HAT complexes. ADA2-GCN5 interaction increases GCN5 binding to acetyl-CoA and stimulates its HAT activity. It remains unclear whether the HAT activity of GCN5 (which acetylates not only histones but also cellular proteins) is regulated by acetyl-CoA levels, which vary greatly in cells under different metabolic and nutrition conditions. Here we show that the ADA2 protein itself is acetylated by GCN5 in rice cells. Lysine acetylation exposes ADA2 to a specific E3 ubiquitin ligase and reduces its protein stability. In rice plants, ADA2 protein accumulation reversely parallels its lysine acetylation and acetyl-CoA levels, both of which are dynamically regulated under varying growth conditions. Stress-induced ADA2 accumulation could stimulate GCN5 HAT activity to compensate for the reduced acetyl-CoA levels for histone acetylation. These results indicate that ADA2 lysine acetylation that senses cellular acetyl-CoA variations is a mechanism to regulate HAT activity and histone acetylation homeostasis in plants under changing environments.

Synthesis of a New Heterocyclic System: Pyrimidine Structural Analogues of Natural Integrastatins A, B

AbstractIn this paper for the first time, we report a simple one-step synthesis of 5-methyl-11,12-dihydro-5H-5,11-epoxybenzo[7,8]oxocino[4,3-d]pyrimidine derivatives by acid-catalyzed cyclization reaction of various 4-methyl-5-acetyl pyrimidine derivatives with salicylic aldehyde. It was shown that 2-substituted 4-methyl-5-acetylpyrimidines successfully react to form a cyclization product. At the same time, 4-methyl-5-acetylpyrimidines with a substituent in the 6th position do not enter into the cyclization reaction. This may be caused by the negative effect of substituents in the 6th position, which hinder the free rotation of the acetyl group and prevent the formation of a stable pre-reaction complex. The structures of the obtained 5-methyl-11,12-dihydro-5H-5,11-epoxybenzo[7,8]oxocino[4,3-d]pyrimidine derivatives were confirmed using 1H NMR and 13C NMR spectroscopy, mass spectrometry, and X-ray diffraction analysis.

Convergent Synthesis of the Nonreducing Hexasaccharide Fragment and the Dodecasaccharide Scaffold of Marine Lipopolysaccharide Axinelloside A.

A convergent synthesis of the dodecasaccharide scaffold of axinelloside A was achieved through Au(I)-catalyzed [6+6] glycosylation. The initially devised [3+1+2] assembly of the nonreducing hexasaccharide fragment was low-yielding, whereas a convergent [3+3] glycosylation under Au(I) catalysis was proven feasible, allowing for a semi-gram scale preparation of the wanted hexasaccharide. The requisite 1,2-cis glycosidic bonds were forged in a highly stereoselective fashion by virtue of remote acetyl group participation, and judicious manipulation of protecting groups. The synthetic dodecasaccharide has been properly protected for the downstream elaboration toward its natural form.

Adaptive mechanism of the marine bacterium Pseudomonas sihuiensis-BFB-6S towards pCO2 variation: Insights into synthesis of extracellular polymeric substances and physiochemical modulation

Marine bacteria can adapt to various extreme environments by the production of extracellular polymeric substances (EPS). Throughout this investigation, impact of variable pCO2 levels on the metabolic activity and physiochemical modulation in EPS matrix of marine bacterium Pseudomonas sihuiensis - BFB-6S was evaluated using a fluorescence microscope, excitation-emission matrix (EEM), 2D-Fourier transform infrared correlation spectroscopy (2D-ATR-FTIR-COS), FT-NMR and TGA-DSC. From the results at higher pCO2 levels, there was a substantial reduction in EPS production by 58–62.8 % (DW). In addition to the biochemical composition of EPS, reduction in carbohydrates (8.7–47.6 %), protein (7.1–91.5 %), and lipids (16.9–68.6 %) content were observed at higher pCO2 levels. Functional discrepancies of fluorophores (tyrosine and tryptophan-like) in EPS, speckled differently in response to variable pCO2. The 2D-ATR-FTIR-COS analysis revealed functional amides (CN, CC, CO bending, -NH bending in amines) of EPS were preferentially altered, which led to the domination of polysaccharides relevant functional groups at higher pCO2. 1H NMR analysis of EPS confirmed the absence of chemical signals from H-C-COOH of proteins, α, β anomeric protons, and acetyl group relevant region at higher pCO2 levels. These findings can contribute new insights into the influence of pCO2 on the adaptation of marine microbes in future ocean acidification scenarios.

Pengembangan Acetylated Cellulose Nanofibers dari Microcrystalline Cellulose: Studi Perubahan Gugus Fungsi dan Indeks Kristalinitas melalui Asetilasi dan Nanofibrilasi

Cellulose nanofiber (CNF) has promising potential as a reinforcement in polymer matrix nanocomposites. CNF is polar or hydrophilic due to having many hydroxyl groups. When CNF particles are combined with a non-polar polymer matrix, the CNF is difficult to distribute evenly and tends to agglomerate due to differences in polarity so that the strengthening effect of CNF is limited. To overcome this problem, it is necessary to chemically modify the CNF surface. Acetylation is one of the most widely used CNF surface modification methods to increase the compatibility between a non-polar polymer matrix and CNF. Through the acetylation process, some of the hydroxyl groups of CNF are replaced with acetyl groups which are hydrophobic. Furthermore, the CNF resulting from the acetylation process is known as acetylated CNF (acetylated cellulose nanofibers or ACNF). The acetylation process is carried out by first mixing microcrystalline cellulose (MCC) particles into 75 mL of acetic anhydride solution. Next, the mixture was stirred using a high-speed blender for 30 minutes for the MCC nanofibrillation process to occur. In this research, the influence of acetylation and nanofibrillation processes on the characteristics of ACNF was studied through studying chemical structure changes using ATR-FTIR and crystallinity index using XRD. The results of the ATR-FTIR analysis show that there are 3 new peaks in the ACNF spectrum, namely at 1720, 1369 and 1203 cm-1, which proves that there is a change in the structure of cellulose after being given acetylation treatment. The results of XRD show that surface treatment of acetylation and nanofibrillation with a high-speed blender increases the ACNF crystallinity index value by 82.53%. Overall, the resulting ACNF has great potential as a reinforcement for polymer matrix nanocomposites.

Top-down ion mobility/mass spectrometry reveals enzyme specificity: Separation and sequencing of isomeric proteoforms.

Enzymatic catalysis is one of the fundamental processes that drives the dynamic landscape of post-translational modifications (PTMs), expanding the structural and functional diversity of proteins. Here, we assessed enzyme specificity using a top-down ion mobility spectrometry (IMS) and tandem mass spectrometry (MS/MS) workflow. We successfully applied trapped IMS (TIMS) to investigate site-specific N-ε-acetylation of lysine residues of full-length histone H4 catalyzed by histone lysine acetyltransferase KAT8. We demonstrate that KAT8 exhibits a preference for N-ε-acetylation of residue K16, while also adding acetyl groups on residues K5 and K8 as the first degree of acetylation. Achieving TIMS resolving power values of up to 300, we fully separated mono-acetylated regioisomers (H4K5ac, H4K8ac, and H4K16ac). Each of these separated regioisomers produce unique MS/MS fragment ions, enabling estimation of their individual mobility distributions and the exact localization of the N-ε-acetylation sites. This study highlights the potential of top-down TIMS-MS/MS for conducting enzymatic assays at the intact protein level and, more generally, for separation and identification of intact isomeric proteoforms and precise PTM localization.

Effect of Direct Alkyne Substitution on the Photophysical Properties of Two Novel Octasubstituted Zinc Phthalocyanines.

The synthesis of two novel phthalonitrile derivatives (3-4) bearing ethynylcyclohex-1-ene and ethynylcyclohexane groups and two peripherally octa substituted zinc (II) phthalocyanines (5-6) were prepared. The synthesis of phthalonitrile derivatives was performed with Sonagashira coupling reaction by using palladium-catalyzed. The newly synthesized compounds were characterized by using FT-IR, NMR, mass, and UV-Vis absorption spectroscopy techniques. Aggregation studies of 5 and 6 were performed in various organic solvents and different concentrations in tetrahydrofuran (THF). The photophysical studies of the Pcs were performed in THF to determine the effect of the alkyne groups on the fluorescence of the Pc ring. Substances showing fluorescence properties can be used in practical applications such as to create an image in microscopy. Fluorescence quantum yield (ΦF) and fluorescence lifetime (τF) of 5-6 were calculated. The fluorescence quenching studies of 5-6 were performed by adding the different concentrations of 1,4-benzoquinone (BQ) to a constant concentration of the Pcs in THF and it was found that benzoquinone was an effective quencher. The values of the Stern-Volmer constant (Ksv) and quenching constant (kq) of zinc phthalocyanines (5-6) were examined. All obtained results were compared with each other and with unsubstituted zinc Pc compound used as a reference.

Ratiometric fluorescent sensing of pyrophosphate with sp³-functionalized single-walled carbon nanotubes

Inorganic pyrophosphate is a key molecule in many biological processes from DNA synthesis to cell metabolism. Here we introduce sp3-functionalized (6,5) single-walled carbon nanotubes (SWNTs) with red-shifted defect emission as near-infrared luminescent probes for the optical detection and quantification of inorganic pyrophosphate. The sensing scheme is based on the immobilization of Cu2+ ions on the SWNT surface promoted by coordination to covalently attached aryl alkyne groups and a triazole complex. The presence of Cu2+ ions on the SWNT surface causes fluorescence quenching via photoinduced electron transfer, which is reversed by copper-complexing analytes such as pyrophosphate. The differences in the fluorescence response of sp3-defect to pristine nanotube emission enables reproducible ratiometric measurements in a wide concentration window. Biocompatible, phospholipid-polyethylene glycol-coated SWNTs with such sp3 defects are employed for the detection of pyrophosphate in cell lysate and for monitoring the progress of DNA synthesis in a polymerase chain reaction. This robust ratiometric and near-infrared luminescent probe for pyrophosphate may serve as a starting point for the rational design of nanotube-based biosensors.

Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology.

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and, as such, provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may result in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn2+. Members of this HDAC group are involved in epigenetic regulation primarily by modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extranuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases, and we will discuss the potential of their inhibitors for lung injury prevention.

Aldehyde and Ketone Hydroboration Mediated by a Heterogeneous Single‐Site Molybdenum‐Dioxo Catalyst: Scope and Mechanistic Implications

AbstractEfficient hydroboration of aldehydes and ketones is demonstrated using a single‐site MoO2 catalyst supported on activated carbon. Under mild conditions with low catalytic loadings, the reaction exhibits chemoselectivity towards carbonyl reduction over halides, alkene, alkyne, nitrile, and ester groups, affording high yields of desired products. Furthermore, competition studies between aldehyde and ketone reduction using HBpin and HBcat indicate that HBpin preferably functionalizes aldehydes, while HBcat can functionalize either substrate under specific conditions. Mechanistic studies suggest that the reaction proceeds via the initial formation of a molybdenum‐hydride species upon B−H activation and subsequent molybdenum‐alkoxide species upon carbonyl activation by the Mo center. The experimental activation energy of 14.3 kcal/mol alignssatisfactorily with the DFT computed ΔH≠ of 18.7 kcal/mol, further supporting the proposed mechanism. Combined experimental/computational analyses reveal that excess HBpin can possibly deactivate the catalyst. The presence of excess benzaldehyde efficiently mitigates deactivation by HBpin, providing significantly higher catalyst recyclability. Overall, this non‐toxic, air‐ and moisture‐stable, active, and selective catalyst demonstrates significant potential for green processes.

Effects of acetyl groups on the prebiotic properties of glucomannan extracted from Artemisia sphaerocephala Krasch seeds

This study explores the structural modification of glucomannan extracted from Artemisia sphaerocephala Krasch seeds (60S) to assess the impact of acetyl groups on its prebiotic characteristics. The structural changes were examined, with a focus on the degree of acetyl group substitution (DS). Both deacetylation and acetylation had limited influence on the molecular properties of 60S. Despite these modifications, the apparent viscosity of all samples remained consistently low. In vitro fermentation experiments revealed that Escherichia-Shigella decreased as DS increased, while Bacteroides ovatus was enriched. Acetylation had no significant impact on the utilization rate of 60S but led to a reduction in the production of propionic acid. Furthermore, untargeted metabolomics analysis confirmed the changes in propionic acid levels. Notably, metabolites such as N-acetyl-L-tyrosine, γ-muricholic acid, and taurocholate were upregulated by acetylated derivatives. Overall, acetyl groups are speculated to play a pivotal role in the prebiotic properties of 60S.

Characteristics and evolution of bioethanol from Manila Tamarind (Pithecellobium dulce) leaf through fermentation

<p>This study's two primary goals are to synthesize bioethanol from biowaste and examine its thermal characteristics. Bioethanol must first undergo a comprehensive assessment of its thermal characteristics in order to be approved for usage in spark-ignition engines. A multi-step procedure comprising extraction, pretreatment, enzymatic hydrolysis, and fermentation was used to manufacture the bioethanol. The raw material was put through a preliminary screening using thermogravimetric analysis to find the mass loss rate as a function of temperature before to starting this process. Remarkably, the Manila tamarind leaves exhibited the highest mass loss, up to 34%. Enzymatic cellulose conversion to fermentable sugars was a critical step in the production of cellulosic ethanol. Following hydrolysis, Saccharomyces cerevisiae was employed in the fermentation process, leading to the bioethanol synthesis phase. The Manila Tamarind leaves yielded the most, around 29% by weight, which is amazing. In order to assess the thermal properties of the extracted ethanol, a variety of parameters were carefully examined, including the viscosity, density, cetane number, and calorific value. In each of these areas, mixtures of tire oil, gasoline, and bioethanol consistently outperformed the others. Furthermore, Fourier Transform Infrared Spectrometry spectra were utilized to validate the concentrations of potential groups, including alcohol, aromatic, alkyne, amide, and carbonyl groups. Clear objectives guide the fermentation process, aiming for consistent quality, safety, and functionality in the end product.</p>

Meroterpenoids from the marine-derived fungus Aspergillus terreus GZU-31-1 exerts anti-liver fibrosis effects by targeting the Nrf2 signaling in vitro

Six undescribed meroterpenoids aspertermeroterpenes A−F and four known analogues were isolated from the marine-derived fungus Aspergillus terreus GZU-31-1. Their structures were elucidated based on spectroscopic methods and electronic circular dichroism calculations. All meroterpenoids possessed the unique acetyl group at C-11, and also aspertermeroterpene A featured the rare C-14 decarboxylated in DMOA meroterpenoids. In the bioassays, aspermeroterpene B exhibited a potent inhibitory effect on the activation of hepatic stellate cells at the concentration of 5 μM via targeting the Nrf2 signaling. This is the first time reported that aspermeroterpene B as a previously undescribed carbon skeleton of meroterpenoid possessed anti-liver fibrosis effect.

Synthesis of sialyl halides with various acyl protective groups

Glycosyl halides are historically one of the first glycosyl donors used in glycosylation reactions, and interest in glycosylation reactions involving this class of glycosyl donors is currently increasing. New methods for their activation have been proposed and effective syntheses of oligosaccharides with their participation have been developed. At the same time, the possibilities of using these approaches to the synthesis of sialosides are restricted by the limited diversity of known sialyl halides (previously, mainly sialyl chlorides, less often sialyl bromides and sialyl fluorides, with acetyl (Ac) groups at the oxygen atoms and AcNH, Ac2N and N3 groups at C-5 were used). This work describes the synthesis of six new N-acetyl- and N-trifluoroacetyl-sialyl chlorides and bromides with O-chloroacetyl and O-trifluoroacetyl protective groups. Preparation of N,O-trifluoroacetyl protected derivatives was made possible due to development of the synthesis of sialic acid methyl ester pentaol with N-trifluoroacetyl group.

Strength evaluation of alkali treated Sabai Grass (Eulaliopsis binata) fibers and its reinforced composites

This investigation aims to use Sabai grass fiber as a substitute reinforcement in epoxy-based composite systems, which is environment friendly and performs similarly to other natural fibers. Composite laminates are prepared with treated and untreated Sabai fibers reinforcement layered in different orientations using vacuum resin transfer molding method. Fabricated composite laminates have been evaluated for their mechanical properties (tensile strength, flexural strength, and impact strength). The effect of varying concentrations (3%, 5%, 7%, and 9 wt.%) of NaOH treatment and fiber reinforcement angle on Sabai fiber-reinforced composite laminates on its physical and mechanical properties are experimentally evaluated. The specimen made with 5 wt.% of NaOH-treated has shown maximum tensile properties because of the higher fiber concentration in the composite laminate. The thickness of fibers gets reduced as the central voids contract after the treatment. The treated strand reinforced (0°/0°/0°/0°) composite laminate has maximum tensile (103.15 MPa) and flexural strength (143 MPa). In addition, it has a higher density (1.20 g/cm3) and less porosity contents (0.70%). The untreated reinforcement has a higher impact strength. The adhesion mechanism at the fiber matrix interface has been studied using field emission scanning electron microscopy by analyzing the fiber surface morphology after treatment and in the fractured samples. The correlation of the mechanical properties of the laminate has been discussed with consideration of interfacial adhesion mechanism, fiber pull-outs, and fiber-matrix cracking phenomenon. FTIR analyses confirm the removal of the peak at around 1735 cm−1 that belongs to the acetyl group of hemicellulose attributed to C=O stretching vibration, and the peak at 1253 cm−1 is associated with the lignin, which is in close agreement with chemical analysis.

Pd-Catalyzed Formal [2 + 2]-Retrocyclization of Cyclobutanols via 2-Fold Csp3-Csp3 Bond Cleavage.

In this work, we describe the unexpected 2-fold Csp3-Csp3 bond cleavage suffered by cyclobutanols in the presence of a catalytic amount of Pd(OAc)2 and promoted by the bulky biaryl JohnPhos ligand. Overall, the sequential cleavage of a strained and an unstrained Csp3-Csp3 bond leads to the formal [2 + 2]-retrocyclization products, namely, styrene and acetophenone derivatives. This procedure might enable the use of cyclobutanols as masked acetyl groups, resisting harsh conditions in organic synthesis.

TREATMENT OF OYSTER SHELLS AND PREPARING THEM AS AN ADSORBENT SURFACE TO TOLUIDINE BLUE DYE

The presence of dyes in drainage water is one of the important problems that many seek to solve. This study included the preparation of the adsorbent surface using the oyster shells as a basis for the preparation of chitosan, which is a series of carbohydrates and saccharides, by treating them with some simple chemical reactions that grab the acetyl group (de-acetylation), which is a part of the structure of chitin. Then the basic formula of Chitosan is ready to carry positive charges, which act as magnet to attract molecules of any substance beside it. A series of assays were undertaken to assess the efficiency of the adsorption process, such as the weight of oyster shells, equilibrium time, effect of pH, initial concentration of toluidine blue dye, and particle size of the adsorbent. These experiments have shown that the equilibrium time was 120 min, the optimum weight of oyster shells was 0.1 g in 100 mL of dye solution, and the particle size was 150 μm. They also showed there is an effect of the pH on the adsorption of the dye. The adsorption isotherm was well fitted to both the Freundlich and Langmuir models.

Synthesis and Characterization of Cellulose Acetate from Oil Palm Empty Fruit Bunches (OPEFB) as Membrane Material

Indonesia is the world’s largest palm oil producer and exporter, can produce 230 kg of OPEFB. The utilization of OPEFB is still at 10%, even though OPEFB is composed of 37.26% cellulose. This research aims to find out how to synthesize and characterize cellulose acetate from OPEFB cellulose into membrane material. The synthesis of cellulose acetate using the acetylation method is carried out in several processes. The activation process expands the surface of the cellulose fibers. The acetylation process is intended to substitute cellulose hydroxyl groups with acetyl groups. The hydrolysis removes some acetyl groups from trimester cellulose and reduces the combination of sulfate esters. In the results of FTIR analysis, carbonyl groups (C=O) and acetyl groups (C-O) have high peak depths in OPEFB cellulose acetate. Based on the calculation of acetyl content, OPEFB cellulose acetate has an acetyl content of 39.82% with a degree of substitution of 2.44. The results of XRD analysis show that OPEFB cellulose acetate has a crystallinity index of 34.5%. In TGA analysis, the thermal stability of cellulose acetate is up to a temperature of 210°C. Based on the research results, OPEFB cellulose can be synthesized into cellulose acetate using the acetylation method.

Study of the microscopic mechanism of stepwise charge injection in co-sensitive DSSCs in the framework of a D-π-A dye and chlorophyll.

The newly synthesized dye molecules TY6 and CXC22 were selected to explain the influence of anthracene and acetylene groups on the power conversion efficiency (PCE) of the molecules at the microscopic level. Theoretical simulation was carried out to understand the properties of the two molecules, including frontier molecular orbitals, absorption spectra, light absorption efficiency, intramolecular charge transfer (ICT), dye regeneration, I-V prediction, etc. The results suggest that for CXC22, adding an anthracene and acetylene group in the conjugate bridge greatly enhances the molecule's absorption wavelength and molar extinction coefficient; CXC22 also has significant advantages in the intramolecular charge transfer and comparatively better dye regeneration and electron injection. These parameters cause CXC22 to have a higher PCE. Subsequently, CXC22 and the chlorophyll molecule (CHL7) were selected for co-sensitization to regulate performance. The stable structure in the co-sensitization configuration was screened, and the absorption spectrum characteristics and charge transfer mechanisms were revealed for the co-sensitization system. The designed evaluation model predicted that the PCE of CO1 (the cosensitive system of CXC22 and TY6 in H-H configuration is referred to as CO1) could reach 16.78%. This work provides an idea for developing an efficient dye-sensitized solar cell system.

Site-specific acetyl modification of 2'-OH of RNA by an oligonucleotide acetylating reagent.

The method for a site-specific RNA acetylation using a novel oligonucleotide acetylating probe (Ac-probe) has been developed. It was confirmed that the acetyl group was site-specifically introduced to a 2'-OH of the sugar part of the target RNA via the formation of the RNA-probe duplex.